In the present grant proposal, the major purpose will be to test whether there is a correspondence between animals and humans in terms of prefrontal cortex mediation of memory function. It has been proposed that the basic deficit in humans with prefrontal cortex damage is the inability to order information on a short-term temporal basis. This is based on both clinical observations and deficits on cognitive tests in which prospective functions dealing with the ability to plan ahead as well as retrospective functions dealing with memory for relative recency are measured. Recently, a behavioral model has been developed in rats in which one can measure (a) memory for order information for a list of places on a maze, (b) memory for a list of temporally based associative relationships between specific stimuli (food cues and places on a maze), and (c) memory for a set of temporally based comparisons between specific stimuli (food cues). I propose to use this animal model as a means of investigating the role of prefrontal cortex in mediating temporal ordering of information. The first aim is to determine whether the medial prefrontal cortex in the rat mediates temporal ordering of information as measured in a variety of tests of cognitive function. The second aim is to determine possible uniqueness of function of the medial prefrontal cortex by examining the role of the orbital-insular prefrontal cortex and the medial-dorsal thalamic projections to the medial and orbital-insular prefrontal cortex. It is hoped that the information gleaned from these studies will provide an understanding of the frontal lobe syndrome such that a rationale therapeutic intervention can be established.